The primary objective of this Mentored Research Scientist Development Award application is to provide mentored training and experience to enable the candidate to transition to an independent career in medical rehabilitation research. The candidate has clinical experience in Occupational Therapy and doctoral and postdoctoral training in the field of motor control and learning. The long-term goal is to become an expert in Movement Neuroscience and Neuroepidemiology. The short term goals during the four-year award include specific training in 1) interval timing control, 2) kinetic analysis of precision grip, 3) biostatistics, particularly regression and analysis of longitudinal data, and 4) Neuroepidemiology and clinical trials related to observational studies, outcome measures, and design of clinical trials. The mentored research program has two aims 1) to investigate mechanisms underlying motor impairments in Huntington's disease (HD) by testing whether they arise due to deficits in interval timing control or deficits in processing sensory feedback. Presymptomatic, symptomatic HD subjects and healthy controls will be tested with a cross-sectional design on two tasks (time reproduction and discrimination & precision grip) that allow for systematic manipulation of temporal and sensory information; 2) to determine the longitudinal rate of change and predictive validity of quantitative motor measures to serve as reliable outcomes for future rehabilitation trials. Presymptomatic, symptomatic HD subjects and controls will be tested on gait, precision grip and functional tasks once a year for three years. Results of this research will help clarify neural mechanisms underlying motor impairments in HD, establish reliable and sensitive markers and provide data for planning a pilot clinical rehabilitation trial. The proposed training and mentored research will facilitate the candidate's transition to an independent researcher in medical rehabilitation. The proposed project is in line with the Institute's priority to understand system responses to physical impairments, functional changes, and developing precise methods of measuring impairments and functional limitations. PUBLIC HEALTH RELEVANCE: The proposed project will help identify fundamental mechanisms that may be amenable to rehabilitation, and provide sensitive and predictive outcome measures for future clinical trials. This methodological approach may be beneficial for other neurodegenerative diseases such as Parkinson's disease and spinocerebellar ataxias.